EU/3/05/313

Orphan designation

On 26 August 2005, orphan designation (EU/3/05/313) was granted by the European Commission to Fondazione Telethon, Italy, for autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene for the treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency.

The sponsorship was transferred to Glaxo Group Limited, United Kingdom, in June 2011 and subsequently to GlaxoSmithKline Trading Services Limited, Ireland, in July 2014.

Update: autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene has been authorised in the EU as Strimvelis since 26 May 2016.

More information on Strimvelis can be found in the European public assessment report (EPAR) on the Agency’s website.

Severe combined immunodeficiency, or SCID, is a group of inherited disorders characterized by little or no body’s defence (immune) response due to the total or partial lack of those specilised white cells (lymphocytes) which are normally part of the body’s defense system. A form of SCID is caused by a lack of adenosine deaminase (ADA), an enzyme (a protein that speeds up the conversion of certain substances into other substances) which helps the cell to clear the waste products it generates during proliferation. This enzyme is important in every cell of the body but in particular in those cells which proliferate rapidly, like the lymphocytes. As a consequence of the adenosine deaminase (ADA) deficiency, lymphocytes, which proliferate greatly during their maturation, are injured by these accumulation of toxic metabolites. This deficiency usually results in the onset of one or more serious infections within the first few months of life. The symptoms of this type of SCID include an increased susceptibility to a variety of infections, including ear infections, lung infections and diarrhea. Because children with SCID experience multiple infections, they fail to grow and to gain weight as expected. Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is chronically debilitating and life-threatening.

At the time of designation, severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 900 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

At the time of submission of the application for the orphan drug designation there were no products authorised in the European Union. Treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency included compatible donor (heterologous) bone-marrow transplantation to replace the defective cells.

The gene coding for the adenosine deaminase enzyme, carried by a so-called “retroviral vector”, is inserted (transfected) into the patient’s own progenitor bone marrow cells (so-called CD34+ cells), previously isolated. It is assumed that, once admininistrated back to the patient, these CD34+ cells transfected with the adenosine deaminase gene will be able to produce their own genetic material (nucleosides) in a normal way and thus actively proliferate in order to restore the normal number of functional white blood cells (lymphocytes).

At the time of submission of the application for orphan designation, clinical trials in patients with severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency were ongoing.

Autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene was not authorised anywhere worldwide for the treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 July 2005 recommending the granting of this designation.

the existence of alternative methods of diagnosis, prevention or treatment;

either the rarity of the condition (affecting not more than 5 in 10,000 people in the European Union) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Review of designation

On 8 April 2016, the Committee for Orphan Medicinal Products (COMP) completed its review of the designation EU/3/05/313 for Strimvelis (autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene) as an orphan medicinal product for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained1.

1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Strimvelis for ‘the treatment of patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available’.

This falls within the scope of the product’s designated orphan indication, which is treatment of severe combined immunodeficiency due to adenosine deaminase deficiency.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2005. ADA-SCID remains a condition that is long-term debilitating and life threatening, because it increases susceptibility to multiple infections and patients rarely survive without treatment beyond 1 or 2 years of age.

The sponsor provided updated information on the prevalence of ADA-SCID based on data from the scientific literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of ADA-SCID remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be 0.04 people in 10,000. This is equivalent to a total of around 2,000 people in the EU.

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Strimvelis still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.